20 - World Journal of Gastroenterology

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tectural distortion associated with irregular hyperplastic lesions [9,10] . Considering the features of architectural distortion, hyperplastic nodules and fibrosis, an attempt was made to classify each liver into one of 4 diagnostic categories, following the terminology for hepatic nodular lesions recommended by an International Working Party and the definitional criteria used by Nakanuma et al [11,12] : idiopathic portal hypertension, diffuse nodular regenerative hyperplasia (NRH), partial nodular transformation, and incomplete septal cirrhosis. Differential diagnosis between these categories is often difficult because single cases frequently do not match the estimated definitions, suggesting that each case of NCPH represents the peculiar pattern of expression of a spectrum of lesions with a common or similar etiopathogenetic background [10] . Here we report a case of NCPH with large regenerative nodules, which highlights the difficulties both in reaching the diagnosis and in classifying the single case into one of the proposed categories. CASE REPORT In July 2009, a 62-year-old Italian man was admitted to the Clinical Medicine and Hepatology Unit of our Hospital for recurrent melena. He had been in good general condition until November 2008, when a first episode of melena occurred in the absence of hematemesis and abdominal pain. Therefore, he was admitted to another hospital, where a severe anemia was found (hemoglobin 5.5 g/dL). A pancolonscopy was negative. Upper intestinal endoscopy showed esophageal varices (not better classified), portal hypertensive gastropathy, and the presence of coagulated blood in the stomach. Upper abdominal ultrasonography revealed hepatomegaly, with caudate lobe hypertrophy, a diffusely dishomogenous echotexture due to the presence of multiple hypoechoic nodules, mainly in the left lobe, the biggest of which was 3 cm in diameter, and mild splenomegaly (transverse diameter: 13.2 cm). Since the patient had no history of chronic liver disease and presented normal liver enzymes and function tests, a transjugular catheterism was performed in order to measure the hepatic pressure venous gradient (HPVG), which confirmed severe portal hypertension (23 mmHg), and to obtain a transjugular liver biopsy, which was negative for cirrhosis-the report of which was the following: “Mild hepatocyte regenerative activity”. The patient had been discharged without a definite diagnosis and with the indication to a strict clinical, biochemical and radiological follow-up. At the admission to our hospital, laboratory tests showed anemia and leucopenia (hemoglobin 9.9 g/dL, hematocrit 32.9%, leucocyte count 2680/μL, platelets 162 000/μL), a good renal function (urea 36 mg/dL, creatinine 0.78 mg/dL), and normal liver enzymes and hepatic function tests: AST 24 U/L [upper normal limit (u.n.l.) 35 U/L], ALT 21 U/L (u.n.l. 45 U/L), alkaline phosphatase 59 U/L (u.n.l. 120 U/L), GGT 18 U/L (u.n.l. 55 U/L), total bilirubin 0.7 mg/dL, total protein 6.6 g/dL, albumin 58%, gamma-globulins 17.1%, INR 1.1. WJG|www.wjgnet.com Vespasiani Gentilucci U et al . Non-cirrhotic portal hypertension: A diagnostic challenge The patient had no history of associated diseases and was not taking any medication. The blood tests performed in the last few years were also reassessed and showed only impaired glucose tolerance and intermittent mild elevation of the GGT (1.5-2 X u.n.l.). Viral serology was negative for hepatitis B surface antigen and antibodies to hepatitis C virus. To rule out autoimmune hepatitis, primary biliary cirrhosis, α-1-antitrypsin deficiency, Wilson’s disease, and hemochromatosis, antinuclear, anti-mitochondrial, anti-smooth muscle, and antiliver and kidney antibodies, α-1-antityripsin, serum iron, transferrin and ferritin, ceruloplasmin, cupremia and cupruria were assessed and found to be negative or within the normal ranges. Also serum α-fetoprotein level was within the normal ranges (1.7 ng/mL, u.n.l. 8.1 ng/mL). Upper intestinal endoscopy confirmed esophageal varices (F2 blue, without cherry red spots, hematocystic spots or diffuse redness, but with red wale markings ++/+++), and severe portal hypertensive gastropathy. Contrast-enhanced computed tomography (CT) and magnetic resonance (MR) of the upper abdomen were performed. On CT, several slightly hypodense liver lesions (almost 10, on both hepatic lobes) were visualized, showing an inhomogeneous contrast uptake due to the presence of a hypodense central core. On MR, liver morphology was not that of a cirrhotic liver. In basal conditions, the hepatic parenchyma was heterogeneous due to the presence of multiple nodules, the biggest of which was 3 cm in diameter, hypointense on T1-weighted sequences and slightly hyperintense on T2-weighted images (Figure 1). Nodules were better represented after gadolinium injection, showing mild signal hyperintensity. The very first radiological impression was that of multiple liver metastases from endocrine tumor, melanoma or renal cell carcinoma. The lesions were also compatible with large regenerative nodules in a radiologically noncirrhotic liver. The hypothesis of hepatocellular carcinoma was also considered, but not supported by the poor hypervascularization in the arterial phase and by the lack of hypointensity in portal venous and delayed phases. In order to rule out malignancy, a US-guided liver biopsy was performed on the 2-cm-sized lesion in the second hepatic segment. Histologically, small foci of necrosis of isolated hepatocytes with focal accumulation of macrophages and other inflammatory cells, and infiltration of portal tracts by scattered mononuclear cells, were observed. The inflammatory infiltrates slightly involved some portal tracts, and were not accompanied by piecemeal necrosis or fibrosis. As recommended in cases of non-cirrhotic portal hypertension, the silver impregnation stain was performed and did not show any architectural alteration. The final histological diagnosis was nonspecific mild chronic hepatitis. In addition, sections from the transjugular liver biopsy performed in the first Hospital were obtained and reassessed by silver impregnation stain (Figure 2). A vaguely nodular arrangement of liver parenchyma was detected, in which areas with hyperplastic hepatocytes, arranged in plates more than one cell thick, were alternated with areas in which the 2581 May 28, 2011|Volume 17|Issue 20|
A B C Vespasiani Gentilucci U et al . Non-cirrhotic portal hypertension: A diagnostic challenge trabeculae were compressed and atrophic. The interface between nodules was not defined by fibrous septa. There was only minimal inflammation and no evidence of degenerative changes of hepatocytes. Histologically, the diagnosis was NRH. Clinically, the diagnosis was NCPH, in the form of NRH associated with large regenerative nodules. As NCPH has been described in association with blood coagulation disorders, myeloproliferative diseases, immunological alterations, systemic or intra-abdominal infections and exposure to toxic substances or to drugs, all these WJG|www.wjgnet.com D Figure 1 Magnetic resonance images before and after gadolinium injection. Half fourier acquisition single shot turbo spin echo T2-weighted sequences showed slightly hyperintense nodules (panel A), which were hypointense on T1-weighted sequences (panel B). After gadolinium injection, lesions were better represented, showing a mild signal hyperintensity (panels C and D). The white arrow in each panel indicates the biggest lesion, 3 cm in transverse diameter, on the caudate lobe. Figure 2 Liver biopsy, reticulin silver impregnation, original magnification, 100 ×. Hyperplastic parenchymal nodules with thickened liver-cell plates are seen (black star), whereas the parenchymal cells adjacent to the nodules are compressed and atrophic (black arrow). This growth pattern is not accompanied by fibrosis. conditions were evaluated and excluded by questioning the patient and performing the appropriate investigations. In particular, the complete panel for hereditary thrombotic risk factors was performed. Lupus anticoagulant, protein-C, protein-S, antithrombin, homocysteine, cardiolipin IgG and IgM antibodies, and anti-β2-glycoprotein-I antibodies were in the normal range. The molecular study was negative for factor V H1299R and G1691A, methylenetetrahydrofolate reductase C677T and A1298C, Plasminogen Activator Inhibitor-1 4G/5G, and for prothrombin G20210A gene polymorphisms. In order to rule out myeloproliferative diseases, the V617F Janus kinase-2 gene mutation was investigated and found to be negative. Bone marrow aspiration was not performed due to the lack of sufficient clinical suspicion justifying the procedure. A first-degree atrioventricular block partially contraindicated beta-blocker therapy and the patient underwent band ligation of esophageal varices. An upper intestinal endoscopy was repeated after one month, revealing persistence of two F1 varices with red wale markings +/+++, which were band-ligated again. A third endoscopic control, performed after another month, was finally negative. At present, after nearly 1 year of follow-up, the patient is in good clinical condition. The last image studies, MR in January 2010 and ultrasonography in June 2010, did not show significant modifications of the hepatic picture. The last upper intestinal endoscopy, performed in August 2010, showed only one F1 esophageal varix without red wale markings, hematocystic spots or diffuse redness. A 2582 May 28, 2011|Volume 17|Issue 20|
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World Journal of Gastroenterology W
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Robert JL Fraser, Daw Park Jacob Ge
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Italy Donato F Altomare, Bari Piero
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Fernando Azpiroz, Barcelona Ramon B
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S Contents EDITORIAL TOPIC HIGHLIGH
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Contents APPENDIX FLYLEAF EDITORS F
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